Clinical trials for transplantation using human derived cells (hNT neurons) have recently been conducted in a limited number of stroke patients with basal ganglia infarction. Preclinical studies using transplantation of fetal kidney tissues or intracebral infusion of glial cell line-derived neurotrophic factor (GDNF) have also demonstrated protective effects against cerebral ischemia. We examined, in the present study, whether such surgical therapy ameliorated deficits associated with chronic cortical stroke in adult Sprague- Dawley rats. One month after right middle cerebral artery (MCA) ligation, animals received transplantation of fetal cortical cells, fetal kidney tissues, fetal kidney + fetal cortical cells, hNT neurons, or vehicle infusion only. In 3 to 7 days after transplantation, all animals, except those that received vehicle infusion, exhibited transient recovery from asymmetrical locomotor activity. Histological assay at two weeks post-transplantation using triphenyltetrazolium chloride (TTC) staining revealed a substantial loss of the right frontal cortex in the animals that received hNT neurons or vehicle infusion. In contrast, surviving cells were detected in the damaged cortices of animals that received fetal cortical cell grafts, fetal kidney tissue grafts, or combination of the two grafts. Previously, we hypothesized that short-term transplantation effects are mediated by release of trophic factors by the grafts. Indeed, ELISA assay of GDNF revealed varying levels of the protein across the three graft sources. The present results suggest that transplantation of GDNF-containing cells/tissues can provide beneficial effects against stroke. [Supported by National Defense Medical Center, Taiwan] - Stroke, Neuroprotection, Transplantation